Sources of Disparities in Surveillance Mammography Performance and Risk-Guided Recommendations for Supplemental Breast Imaging: A Simulation Study.

BACKGROUND: Surveillance mammography is recommended for all women with a history of breast cancer. Risk-guided surveillance incorporating advanced imaging modalities based on individual risk of a second cancer could improve cancer detection. However, personalized surveillance may also amplify disparities. METHODS: In simulated populations using inputs from the Breast Cancer Surveillance Consortium (BCSC), we investigated race- and ethnicity-based disparities. Disparities were decomposed into those due to primary breast cancer and treatment characteristics, social determinants of health (SDOH) and differential error in second cancer ascertainment by modeling populations with or without variation across race and ethnicity in the distribution of these characteristics. We estimated effects of disparities on mammography performance and supplemental imaging recommendations stratified by race and ethnicity. RESULTS: In simulated cohorts based on 65,446 BCSC surveillance mammograms, when only cancer characteristics varied by race and ethnicity, mammograms for Black women had lower sensitivity compared with the overall population (64.1% vs. 71.1%). Differences between Black women and the overall population were larger when both cancer characteristics and SDOH varied by race and ethnicity (53.8% vs. 71.1%). Basing supplemental imaging recommendations on high predicted second cancer risk resulted in less frequent recommendations for Hispanic (6.7%) and Asian/Pacific Islander women (6.4%) compared with the overall population (10.0%). CONCLUSIONS: Variation in cancer characteristics and SDOH led to disparities in surveillance mammography performance and recommendations for supplemental imaging. IMPACT: Risk-guided surveillance imaging may exacerbate disparities. Decision-makers should consider implications for equity in cancer outcomes resulting from implementing risk-guided screening programs. See related In the Spotlight, p. 1479.

Leveraging TCGA gene expression data to build predictive models for cancer drug response.

BACKGROUND: Machine learning has been utilized to predict cancer drug response from multi-omics data generated from sensitivities of cancer cell lines to different therapeutic compounds. Here, we build machine learning models using gene expression data from patients' primary tumor tissues to predict whether a patient will respond positively or negatively to two chemotherapeutics: 5-Fluorouracil and Gemcitabine. RESULTS: We focused on 5-Fluorouracil and Gemcitabine because based on our exclusion criteria, they provide the largest numbers of patients within TCGA. Normalized gene expression data were clustered and used as the input features for the study. We used matching clinical trial data to ascertain the response of these patients via multiple classification methods. Multiple clustering and classification methods were compared for prediction accuracy of drug response. Clara and random forest were found to be the best clustering and classification methods, respectively. The results show our models predict with up to 86% accuracy; despite the study's limitation of sample size. We also found the genes most informative for predicting drug response were enriched in well-known cancer signaling pathways and highlighted their potential significance in chemotherapy prognosis. CONCLUSIONS: Primary tumor gene expression is a good predictor of cancer drug response. Investment in larger datasets containing both patient gene expression and drug response is needed to support future work of machine learning models. Ultimately, such predictive models may aid oncologists with making critical treatment decisions.